Summary of Work: It is hypothesized that epoxide intermediates play a role in the pathogenesis of hemangiosarcomas by causing genetic alterations in tumor suppressor genes and proto-oncogenes. Preliminary data has shown that chloroprene induced hemangiosarcomas have elevated p53 protein and specific point mutations have been detected in exon 5-8. Chemically induced hemangiosarcomas in 1, 3 butadiene o-nitrotoluene, riddelliine and tetrafluoroethylene studies are being evaluated for specific genetic alterations in the P53 gene. Tumor suppressor gene and oncogene analysis will provide valuable information on the relationship between carcinogen exposure and DNA damage and the relevance to humans.